Figure 4.

Sensitization of TRPV1 by PAR activation. A - D. Heat-activated currents were significantly enhanced in c. 10% of neurons
by application of PAR1-AP and PAR4-AP. Single traces in panels to left are taken from
time courses shown in right hand panels. Both PAR1-AP (TFLLR at 100 μM) and PAR4-AP
(AYPGKF, 200 μM) caused long-lasting sensitisation. Sensitization showed complete
tachyphylaxis on a second application.

E. Percentage sensitization in experiments similar to those in A. Thrombin (100 nM),
trypsin (100 nM), PAR1-AP and PAR4-AP all caused approximately a doubling of the inward
current elicited by heat. Thrombin-induced sensitisation was largely blocked by the
PKC inhibitor Ro318220 (1 μM) and by the broad-spectrum kinase inhibitor staurosporine
(1 μM, both applied throughout the experiment).